Cytolysis

Cytolysis

An important immune function involving the dissolution of certain cells. There are a number of different cytolytic cells within the immune system that are capable of lysing a broad range of cells. The most thoroughly studied of these cells are the cytotoxic lymphocytes, which appear to be derived from different cell lineages and may employ a variety of lytic mechanisms. Cytotoxic cells are believed to be essential for the elimination of oncogenically or virally altered cells, but they can also play a detrimental role by mediating graft rejection or autoimmune disease. There are two issues regarding cytotoxic lymphocytes that are of concern: one is the target structure that is being recognized on the target cell, that is, the cell that is killed, which triggers the response; and the other is the lytic mechanism. SeeCellular immunology

When freshly isolated, large granular lymphocytes from peripheral blood are tested in cytotoxicity assays, they spontaneously lyse certain tumor cells. These cytotoxic cells are called natural killer cells, and they are important mediators of innate immunity as a first line of defense against invading pathogens. They are unique in that no previous sensitization is required for them to kill. It now appears that a number of different receptors on natural killer cells are capable of activating the lytic machinery. Recently, it has been found that these cells also express inhibitory receptors that actually inhibit cell lysis, thus adding another level of complexity to the regulation of cytolysis by these cells.

Another killer cell, called the lymphokine-activated killer cell can lyse any target cell, including cells from freshly isolated tumors, and are employed in cancer therapy. Lymphokine-activated killer cells may also be important in mounting a vigorous response under conditions of extreme immunological stress. Very little is known about the mechanisms by which these cells recognize and lyse the target cell.

The last group of cytotoxic cells is the cytotoxic T lymphocyte. These are T cells that can lyse any target cell in an antigen-specific fashion. That is, as a population they are capable of lysing a wide range of target cells, but an individual cytotoxic T lymphocyte is capable of lysing only those target cells which bear the appropriate antigen. These are truly immune cells in that they require prior sensitization in order to function. These cells are thought to mediate graft rejection, mount responses against viral infections and intracellular bacterial infections, and play a major role in tumor destruction.

Cytotoxic cell-mediated lysis is divided into three distinct steps. The first step is conjugation, when the killer cell determines if the target cell expresses the appropriate antigen and binds to it via a complex array of adhesion molecules. The second step involves the programming for lysis in which the lytic event is triggered. The third step is the destruction of the target cell.

Direct cell contact between the target cell and the killer cell is absolutely required for initiating the lytic mechanism. Killer cells remain unscathed during the lytic event, suggesting that the killer cell must either employ a unidirectional lytic mechanism or be resistant to the lytic mechanism. Also, when many, but not all, target cells die after cytotoxic T-lymphocyte interaction, nuclear damage with rapid DNA fragmentation precedes detectable plasma membrane damage. SeeAntigen, Histocompatibility

It is becoming clear that cytotoxic lymphocytes employ multiple mechanisms designed to initiate target cell destruction. If cytolysis exists to protect the organism from invading pathogens, there should be redundancies in the system so that, if the pathogen has a mechanism for escaping one cytolytic pathway, alternative mechanisms would still be functional. Two mechanisms are the degranulation of cytolytic granules and the triggering of death receptors found on target cells. In the degranulation mechanism of killing, cytotoxic cells release the contents of cytotoxic granules after specific interaction with the target cell. This results in the leakage of salts, nucleotides, and proteins from the target cell, leading to cell death.

On virtually all cells of the body a number of receptors have been identified that are able to trigger apoptosis when engaged. These receptors are called death receptors. The most studied, and relevant to cytolytic cells, is a receptor called Fas. Fas, when engaged by its ligand (FasL), triggers the caspase cascade leading to the hallmark signs of apoptosis, which include membrane blebbing, chromosomal condensation, nuclear disintegration, DNA fragmentation, and cell death.

Cytolysis

the destruction of animal and plant cells by complete or partial dissolution. Lysosomes, which are intracellular structures, play an active part in cytolysis. They contain enzymes that split the high-molecular-weight components of the cell, such as proteins, nucleic acids, polysaccharides, and lipids. Cytolysis occurs under normal physiological conditions, as in metamorphosis, and in a variety of pathological states. (For additional information, seeLYSOSOMES and .)

cytolysis

[sī′täl·ə·səs]

(pathology)

Disintegration or dissolution of cells, usually associated with a pathologic process.

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